Stichting Onderzoek Cancer Center Amsterdam

Rationale: In patients with chronic lung diseases, the role of respiratory muscle dysfunction has been underestimated. Also, current treatment options, like chronic NIV and lung transplantation (LTx), might also have deleterious effects on the respiratory muscles, and the mechanisms are poorly understood.
Therefore in this exploratory study the objectives are to:
1. Determine in vivo respiratory muscle function and progression of respiratory muscle dys-function in end-stage COPD patients
2. Establish the correlation between changes in the structure and contractility of respiratory myofibers and in vivo respiratory muscle function.
3. Establish the effect of chronic NIV on structure and contractility of respiratory muscle fi-bers
4. Determine whether the structure and contractility of respiratory muscles cells at the time of LTx predicts clinical recovery post-LTx.
Study design: The study will be an exploratory observational cohort study following patients on the LTx waiting list during the waiting period and afterwards until they showed functional recovery of respiratory muscle function.
Study population: Adult COPD patients on the LTx waiting list will be included. Intervention (if applicable): None
Main study parameters/endpoints:
To assess clinical functioning of the respiratory muscles we will assess respiratory electrical activity as a measure of respiratory effort by surface EMG, and thickening fraction of the diaphragm and intercostal muscles and diaphragm excursions by ultrasound and maximal in- and expiratory pressure to assess muscle output; all before and after LTx. We will relate and correct these data for hyperinflation and degree of lung damage by using data from standard care lung function tests and CT scans, and will relate these measurements to prior treatment (NIV settings) and outcome after LTx, by retrieving these data from the EPD.
To assess contractility of respiratory myofibers and in vivo respiratory muscle function, biopsies will be taken during LTx surgery and the biopsies will be analyzed in the lab of Prof. Ottenheijm (AmsterdamUMC) for individual myofiber functioning (strength, calcium sensitivity, myofiber characteristics) and in the lab of Dr. Pouwels for extracellular matrix characteristics.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Overall, risks are believed to be minimal. The clinical measurements are non-invasive and/or regular performed in clinical practice. Also, we decided to do those measurements during regular control visits, limiting the burden for the patients. Taking biopsies from the respiratory muscles during surgery has been extensively performed without any risk; the biobank of the Ottenheijm group contains > 500 samples and never any complication has been observed. Also, in preparation of the present study we performed a pilot study in 12 COPD patients of whom.. biopsies were taken at the UMCG without side effects or complications. The biopsies will be done with the patients being under full anesthesia, so participants will feel no discomfort.

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